Previous research results from our own and other laboratories have established an association of increased histaminase levels with a number of human cancers. Based on this association and the fact that the enzyme is produced at high level in placenta but at very low level in most normal tissues, research efforts have been made in our laboratory to establish histaminase as a onco-placental enzyme. This is carried out by the comparison of the biochemical and immunological characteristics of this enzyme from the placenta and from malignant effusion fluids and tumors. A monospecific anti-serum against placental histaminase reacts with the enzyme in tumors and in malignant effusion fluids. Using this antiserum, immunohistochemical staining methods for this enzyme have been developed. We now propose to further evaluate the potential of histaminase as a biochemical marker for human cancer. This will be done by first developing a sensitive radioimmunoassay for histaminase. Using this method, together with the immunohistochemical methods, we will study this enzyme in sera, malignant effusion fluids, tumor cells and tumor tissues of cancers of various types at various stages of the disease. Results will be evaluated for the correlation of the presence of this enzyme with the type and the stage of the cancer and with the histopathological characteristics of the tumor. Biochemical and immunological studies of this enzyme in placenta and in tumor will be carried out to obtain basic information pertinent to the understanding of the significance of this enzyme in normal and in tumor cells. This study, if successfully accomplished, will be a major step toward the development of a test using histaminase for the detection and monitoring of the cancer.